Search

To present the prenatal features and postnatal outcomes of pregnancies with fetal nemaline myopathy (NM). This was a retrospective study of nine cases with NM diagnosed by prenatal or postnatal clinical features and confirmed by genetic testing. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, exome sequencing (ES) results, and pregnancy outcomes. All of the nine cases were detected to have NM-causing variants, involving NEB gene in 2 cases, ACTA1 in 3 cases, KLHL40 in 3 cases, and TPM2 in 1 case. Almost all (8/9) had normal first-trimester ultrasound scans except one who had an increased nuchal translucency. Seven (7/9) cases had second-trimester abnormal ultrasounds with fetal akinesia and/or extremity anomalies. Two (2/9) had only third-trimester abnormal ultrasounds with fetal akinesia and polyhydramnios, with one combined with fetal growth restriction. Four pregnancies with a positive prenatal ES were terminated, while five having not receiving prenatal ES continued to term. Only one infant survived 1 year old, and four passed away within 12 months. Prenatal ultrasound can detect clues that lead to the diagnosis of NM, such as reduced or absent fetal movements, polyhydramnios and extremity anomalies. [ABSTRACT FROM AUTHOR]

• Prenatal ultrasound-based diagnosis of epidermolysis bullosa is difficult, but not impossible. Several sonographic signs, even if nonspecific, are more frequently reported in the few cases described in literature to date. • The prenatal ultrasound confirms a good level of accuracy in assessing fetuses with suspicion of epidermolysis bullosa. • This paper suggests for future investigations to carefully evaluate the muco-cutaneus areas, including the perioral area. The fetal mobility and the 3D ultrasound should be part if the examination. This is the first systematic review specifically focused on prenatal ultrasound signs of EB. Epidermolysis bullosa is a rare hereditary autosomal disease that is included in the heterogeneous group of genodermatosis. It is characterized by skin and mucous membranes fragility and denudation, and it can be associated with pyloric atresia. Prognosis is often poor, and death can occur in neonatal period due to severe sepsis. We present a case of fetal junctional epidermolysis bullosa in a consanguineous couple, highly suggested by previous obstetric history and several antenatal ultrasound signs, such as polyhydramnios, gastric enlargment, the "snowflake sign", abnormal external ears, signs of skin desquamation, lower limbs anomalies and chorioamniotic membrane separation. We describe a marked perioral hipoecogenicity as a novel sign of skin-mucous denudation, which could be helpful for future diagnosis. A review of literature, focused specifically on the antenatal sonography role, is also reported. Prenatal ultrasound-based diagnosis of epidermolysis bullosa is difficult, especially in apparently low risk contexts, but may be possible. [ABSTRACT FROM AUTHOR]

Objective: To determine the fetal ultrasound findings associated with Sotos syndrome caused by deletions at 5q35 including the NSD1 and a point mutation in this gene.Study Design: This was a retrospective study of eight pregnancies with fetal Sotos syndrome identified by chromosomal microarray (CMA)/whole exome sequencing (WES). Clinical and laboratory data were collected and reviewed for these cases.Results: Two cases had no significant fetal abnormalities, and were only diagnosed after birth. One case presented in the first trimester with increased nuchal translucency. The remaining five fetuses were identified at late gestation. One of the five fetuses presented in the second trimester with mild ventriculomegaly, and four in the third trimester with mild ventriculomegaly, macrocephaly and polyhydramnios. CMA was done on all cases and revealed 5q35 deletions in seven cases, and WES detected a maternally inherited NSD1 variant in one case.Conclusion: The fetal ultrasound findings in cases with Sotos syndrome, associated with deletions at 5q35 and a point mutation in the NSD1 are not specific with the most common finding being mild ventriculomegaly. [ABSTRACT FROM AUTHOR]

Objective: To present the experience on prenatal diagnosis of Miller-Dieker syndrome (MDS)/PAFAH1B1-related lissencephaly to further determine fetal phenotypes of this syndrome.Study Design: This was a retrospective study of ten pregnancies with fetal MDS/PAFAH1B1-related lissencephaly identified by chromosomal microarray (CMA)/exome sequencing (ES). Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, CMA or ES results and pregnancy outcomes.Results: Two cases were diagnosed in the first trimester because of an increased nuchal translucency. The remaining eight cases were identified at late gestation, including four in the second trimester because of fetal cardiac anomalies or ventriculomegaly, and four in the third trimester because of ventriculomegaly. CMA revealed 17p13.3 deletions in nine cases, and ES detected a de novo PAFAH1B1 missense mutation in one case.Conclusion: The prenatal presentation of MDS/PAFAH1B1-related lissencephaly depended on the gestational age when the diagnosis was made. Mild ventriculomegaly was the most common prenatal sonographic sign identified in cases of MDS/PAFAH1B1-related lissencephaly. It is important that fetal MRI and invasive testing with CMA should be considered in fetuses with apparently 'isolated' mild ventriculomegaly. [ABSTRACT FROM AUTHOR]

Objective: This study aims to assess accuracy and clinical utility of postmortem radiological exams [Magnetic Resonance Imaging (MRI), Computed Tomography (CT) and Radiography (XR)] after termination of pregnancy at <23 weeks' gestation for congenital fetal malformations in comparison to autopsy.Study Design: This a prospective single-center study on fetuses underwent termination of pregnancy for fetal defects. Overall concordance between any radiological exam and autopsy was evaluated. For postmortem MRI only, the following subgroups were analyzed: 1) total agreement; 2) agreement for main findings; 3) agreement for main findings but major relevant additional findings at autopsy; 4) total disagreement.Results: 174 cases were collected. The overall concordance with autopsy for main findings was 71% (115/163) for postmortem MRI and 99% (173/174) for prenatal ultrasound (US). Postmortem MRI detection rate was high for central nervous system (CNS) defects (98%), gastrointestinal, genitourinary and respiratory defects (100%), while it was poor for cardiovascular and musculoskeletal defects (25% and 42%, respectively). For musculoskeletal abnormalities, the performance of postmortem XR and postmortem CT exams improved the detection rate from 42% for postmortem MRI alone to 92%.Conclusions: Postmortem MRI has a good overall concordance for fetal defects after termination of pregnancy performed at <23 weeks. Along with autopsy, postmortem MRI may be offered for all cases of CNS defects in order to prevent inconclusive exams due to autolysis of the brain tissue, while postmortem CT and postmortem XR are indicated for musculoskeletal defects. In the presence of multiple abnormalities or cardiac defects the couple should be counseled on the poor performance of radiological investigations. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to report the rate of additional anomalies detected exclusively at prenatal magnetic resonance imaging (MRI) in fetuses with isolated severe ventriculomegaly undergoing neurosonography.Method: Multicenter, retrospective, cohort study involving 20 referral fetal medicine centers in Italy, United Kingdom, Spain and Denmark. Inclusion criteria were fetuses affected by isolated severe ventriculomegaly (≥15 mm), defined as ventriculomegaly with normal karyotype and no other additional central nervous system (CNS) and extra-CNS anomalies on ultrasound. In all cases, a multiplanar assessment of fetal brain as suggested by ISUOG guidelines on fetal neurosonography had been performed. The primary outcome was the rate of additional CNS anomalies detected exclusively at fetal MRI within two weeks from neurosonography. Subgroup analyses according to gestational age at MRI (Results: 187 fetuses with a prenatal diagnosis of isolated severe ventriculomegaly on neurosonography were included in the analysis. Additional structural anomalies were detected exclusively at prenatal MRI in 18.1% of cases. When considering the type of anomaly, malformations of cortical development were detected on MRI in 32.4% cases, while midline or acquired (hypoxemic/hemorrhagic) lesions were detected in 26.5% and 14.7% of cases, respectively. There was no difference in the rate of additional anomalies when stratifying the analysis according to either gestational age at MRI or laterality of the lesion. At multivariate logistic regression analysis, the presence of additional anomalies only found at MRI was significantly higher in bilateral compared versus unilateral ventriculomegaly (OR: 4.37, 95% CI 1.21-15.76; p = 0.04), while neither maternal body mass index, age, severity of ventricular dilatation, interval between ultrasound and MRI, nor gestational age at MRI were associated with the likelihood of detecting associated anomalies at MRI.Conclusion: The rate of associated anomalies detected exclusively at prenatal MRI in fetuses with isolated severe ventriculomegaly is lower than previously reported, but higher compared to isolated mild and moderate ventriculomegaly. Fetal MRI should be considered as a part of the prenatal assessment of fetuses presenting with isolated severe ventriculomegaly at neurosonography. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prognosis of fetuses with a prenatal diagnosis of micrognathia in the first trimester.Study Design: Over a 3-year period, patients with fetal micrognathia were detected at the time of nuchal translucency screening. The medical records of these pregnancies were reviewed, including maternal demographics, sonographic findings, genetic testing results and pregnancy outcomes.Results: Forty-three cases of first-trimester micrognathia were included in this study. Chromosomal abnormalities were detected in seven cases. Of the fetuses with a normal array, further investigation of monogenic disorders with whole-exome sequencing was undertaken in 13 cases. Monogenic syndromes were identified in eight cases, including six with de-novo dominant alleles and two with recessive conditions. Whole-exome sequencing was refused in 23 cases; among these, other additional anomalies were found on anatomic ultrasound in 10 cases.Conclusion: This study demonstrated that caution should be adopted when finding an apparently isolated micrognathia in early gestation, even with a normal array. A diagnosis of genetic syndrome or multiple anomalies on subsequent scans is most likely, and will affect the final prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Alongside initial screening obstetric US, use of placental MRI has been increasing in the last few decades to aid with antenatal diagnosis and delivery planning in Placenta Accreta Spectrum (PAS). The aim of this study was to determine if the MRI pathophysiological sign subcategories described in the current literature can predict the severity of pathologic diagnosis.Methods: Institutional imaging records were reviewed for placental MRIs performed for suspicion of PAS in the last decade. Electronic health records were searched for patient history and pathology. The 59 MRI studies were reviewed using the 11 MRI signs described by the SAR and ESUR joint consensus statement. Further breakdown of the signs was divided by underlying pathophysiologic subcategories including gross morphologic, interface and tissue architecture signs.Results: Pathologic diagnosis yielded 34 cases: accreta 4/34, incerta 14/34, percreta 10/34 and normal 6/34. Of the accreta cases all of them demonstrated at least two interface and half of the cases had tissue architecture signs, 13/14 increta cases demonstrated interface signs and 12/14 demonstrated tissue architecture signs, 9/10 percreta cases had two interface and at least six demonstrated three tissue architecture signs. Statistical analysis showed significant difference between pathologic diagnosis and the number of positive interface signs with p = 0.02.Discussion: Interface signs were the most objective and sensitive MRI subcategory. Statistical analysis determined there was a significant difference between PAS diagnosis and number of interface signs present. This subcategory has the most overlap with classic US signs which are traditionally used before MRI referral. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical application of medical exome sequencing (MES) for prenatal diagnosis of genetic diseases related to fetal structural anomalies detected by prenatal ultrasound examination.Study Design: A total of 105 fetuses with structural anomalies were negative results in both Quantitative fluorescent polymerase chain reaction (QF-PCR) and chromosomal microarray analysis (CMA). Then trio-based MES was further used for identifying the potential monogenic diseases in these fetuses. Coding regions and known pathogenic non-coding regions of over 4000 disease-related genes were interrogated, and variants were classified following the guidelines of American College of Medical Genetics (ACMG).Results: The 105 fetuses with structural anomalies were categorized into 12 phenotypic groups. A definitive diagnosis was achieved in 19% (20/105) of the cases, with the identification of 21 pathogenic or likely pathogenic variants in 14 genes. The proportion of patients with diagnostic genetic variants varied between the phenotypic groups, with the highest diagnostic yield in the cardiovascular abnormalities (44%), followed by the skeletal and limb abnormalities (38%) and brain structural abnormalities (25%). In addition, 12 fetuses were detected variants of unknown significance (VOUS), while the relevance of phenotypes and variants would further evaluated.Conclusion: MES can identify the underlying genetic cause in fetal structural anomalies. It can further assist the management of pregnancy and genetic counseling. It was demonstrated the importance of translating prenatal MES into clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To assess the diagnostic accuracy of prenatal ultrasound for detecting fetal skeletal dysplasias and to describe its role in orienting genetic studies.Study Design: Observational study of pregnant women surveyed in our hospital, between 2011 and 2018, with fetal long bones below the 3rd centile (shortened long bones), either as an isolated finding or associated to other skeletal anomalies. We used a systematic protocol for the ultrasound evaluation and selection of those fetuses suspected of having a skeletal dysplasia. We report the demographics of these patients along with the sonographic follow-up of their fetuses, the genetic results and the outcome of the pregnancies and the newborn in the entire group and also compare data between the two sub-groups (isolated shortened long bones vs shortened long bones associated to other anomalies).Results: A total of 81 pregnancies with a suspected fetal skeletal dysplasia were included, with a complete follow-up available in 75 cases, 22 with isolated shortened long bones and 53 cases that presented shortened long bones with other skeletal anomalies. In the shortened long bones sub-group, a total of five (23 %) were born healthy neonates, 10 (45 %) were small for gestational age or intrauterine growth restricted (one of them of genetic origin) and seven (32 %) had a skeletal dysplasia (6 of them with genetic diagnosis). Whilst among the 53 cases that presented with shortened long bones + other skeletal anomalies, three (6%) were healthy neonates, five (9%) were small for gestational age/intrauterine growth restricted (two of genetic origin) and 45 (85 %) had a skeletal dysplasia (19 genetically confirmed and 26 with a clinical diagnosis). These differences in frequencies between the two sub-groups were determined to be statistically significant (χ2: p = 0.02).Conclusion: Around one third of fetuses with isolated shortened long bones will have a skeletal dysplasia. If abnormal skeletal ultrasound findings are associated with shortened long bones, the risk for skeletal dysplasia is significantly increased (85 %). Prenatal systematic approach in a multidisciplinary unit is useful in the orientation of genetic studies. [ABSTRACT FROM AUTHOR]

Objective: To share our experience in diagnosis of congenital central nervous system (CNS) abnormalities by fetal magnetic resonance imaging (MRI).Study Design: This study consisted of 110 pregnancies. Neurosonography (NS) findings were compared with MRI results. Anomalies were categorized into 10 groups: 1) Corpus callosum (CC) and cavum septum pellucidum (CSP) anomalies, 2) Neural tube defects (NTD), 3) Posterior fossa anomalies (PFA), 4) Primary ventriculomegaly (PVM), 5) Microcephaly, 6) Macrocephaly, 7) Periventricular leukomalacia (PVL), 8) Craniosynostosis, 9) Intracranial hemorrhage (ICH) and 10) Lumbosacral teratoma. Demographic features, clinical characteristics and perinatal outcomes of the study subjects were evaluated.Results: Gestational weeks for NS and for MRI were 25.5 and 26.5 weeks, respectively. Fourteen (12.7%) pregnancies were terminated. PVM (n = 36, 32.7%), CC and CSP anomalies (n = 29, 26.3%), PFA (n = 11, 10%) and NTD (n = 11, 10%) were the most common fetal MRI indications. There were no statistically significant differences between the accuracy of fetal NS and fetal MRI for CC and CSP anomalies, NTDs, PFA and PVM (p = 0.09, 0.43, 0.45 and 0.23, respectively). However, fetal MRI was more accurate for the detection of normal anatomic findings in cases with suspected microcephaly, macrocephaly and craniosynostosis in NS when pooled together (p = 0.007). Furthermore, MRI also seemed to be advantageous in CC & CSP anomalies though it was not validated by statistical measures. No statistically significant difference was found for diagnostic performance of NS and MRI according to gestational week (p = 0.27).Conclusion: Fetal MRI in addition to NS may improve diagnostic accuracy in pregnancies with congenital CNS abnormalities. [ABSTRACT FROM AUTHOR]

Objectives: To test the equivalence of two fetal weight estimation formulas generated by Hadlock, a formula that includes head circumference parameter (H1), and another (H2) which excludes this parameter. A secondary aim was to identify the patients in which H2 formula is less reliable to use.Study Design: This retrospective cohort study included a total of 1220 sonographic fetal weight estimations performed within seven days of delivery and recorded at a single medical center from January 2014 to December 2016. Estimated fetal weight was calculated using H1 and H2 formulas. Their accuracies were compared using percentage error, the proportion of weight estimations falling within ±15% error interval and by Bland-Altman analysis. Multivariate regression was performed to evaluate factors affecting weight estimation by H2 formula.Results: The mean birth weight was 3288.92 ± 641.27gr. The H2 formula presented with statistically significant higher value of systemic mean percent error comparing to H1 (3.19% vs. 1.87%, p < 0.001 respectively). H2 formula had a lower accuracy compared to H1 in predicting fetal weight within ±15% of birth weight (90.49% vs. 93.44%, p < 0.01 respectively). Using Bland-Altman analysis, the 95% limits of agreement between both formulas were (-142.03) to 231.79gr with a mean of 44.88gr. Factors found to influence significantly on H2 formula were long femur length (OR 1.144, p < 0.0001) and low maternal age (OR 0.947, p < 0.01).Conclusions: H1formula was more accurate than H2 formula in predicting fetal weight at term. However, the accuracy difference was found to be small. Therefore, if ultrasonographic evaluation of HC is technically difficult, Hadlock formula that excludes head circumference can be used with confidence. Caution should be paid with higher values of femur length and lower maternal age. [ABSTRACT FROM AUTHOR]

Fetal lymphangioma is a rare congenital malformation of lymphatic system that involve the skin and the subcutaneous tissue. The vast majority of the lymphangioma occurs in the neck. More rarely lymphangiomas may occur in the axillary region, including chest wall. Our consecutive case series study included three cases of fetal chest wall cystic lymphangiomas. In our cohort, fetal chest wall cystic lymphangiomas were the 18.8% of the all cases of lymphangiomas of axillary region. In all the three cases no other fetal abnormalities were evaluated, and the chest wall cystic lymphangiomas were unilateral, honeycombed in appearance, with multiple echo-free area of varying size in the mass, with no color flow on Doppler sonography, and with a trend to increase during the gestation. The incidence of chromosomal abnormalities was 33.3%, with one case out of the three being trisomy 21.The literature review revealed only seven cases of fetal chest wall cystic lymphangiomas. The cases were not associated with other abnormalities, nor with abnormal karyotype and only one case of fetal death was reported. Three women delivered vaginally. In summary, fetal chest wall cystic lymphangioma is a very rare malformations with only seven cases reported in the literature. This malformation is usually not associated with abnormal karyotype or other abnormalities and the neonatal outcome is favorable after surgical removal. Spontaneous vaginal delivery may be a safe approach for delivery women with fetal chest wall cystic lymphangioma. CONDENSATION: Fetal chest wall cystic lymphangioma is a very rare malformations with only seven cases reported in the literature. This malformation is usually not associated with abnormal karyotype or other abnormalities and the neonatal outcome is favorable after surgical removal. Spontaneous vaginal delivery may be a safe approach for delivery women with fetal chest wall cystic lymphangioma. [ABSTRACT FROM AUTHOR]

Objective: Congenital heart defects are the most common major structural fetal abnormalities. Color flow mapping has played a dominant role in the detection of abnormalities during the first trimester, regardless of the International Society of Ultrasound in Obstetrics and Gynecology warning on the use of Doppler during early pregnancy. The aim of our study was to investigate the use of transvaginal two-dimensional sonography without Doppler for assessing the four-chamber view and the outflow tract view of fetuses at 11-13 weeks of gestation for cardiac screening of major congenital heart defects.Study Design: This was a prospective observational study conducted in the Fetal Medicine Unit of Cabueñes University Hospital, between May 2014 and August 2015. Only low risk-pregnancies were studied. All ultrasonographic examinations were performed by two experienced sonographers in maternal-fetal medicine. The combination of high-frequency transvaginal (nine MHz) and transabdominal (six MHz) ultrasonography transducers were used. An early cardiac screening was performed in 97% of cases. Statistical analysis was carried out using successive multivariate logistic regression models in order to investigate the effect of crown-rump length and body mass index on the probability of visualizing the four-chamber view and/or the outflow tract view.Results: 663 low-risk pregnant women were included. Regarding the transvaginal approach, neither the crown-rump length nor the body mass index had a statistically significant relationship on the probability of visualization of the four-chamber view and outflow tract view. For the transabdominal approach, the crown-rump length and the body mass index presented a statistically significant effect on the visualization of the four-chamber view and the outflow tract view. Using the transvaginal approach: the success rate of performing a four-chamber view was 89.4% and 82.4% for the outflow tract view. Using the transabdominal approach: the success rate of performing a four-chamber view was 77.8% and 61.5% for the outflow tract view. Four major congenital heart defects were diagnosed, and the prenatal ultrasonagraphic diagnosis was confirmed for all cases.Conclusions: Routine first-trimester ultrasonagraphy without Doppler, when performed by experienced sonographers, can effectively identify major congenital heart defects. Additional multicenter well designed studies should clarify the feasibility of this approach. [ABSTRACT FROM AUTHOR]

Objective: This retrospective study aims to evaluate the incidence, presence of chromosomal anomalies and outcome of fetuses diagnosed with cystic hygroma colli in the first trimester in a single tertiary center.Study Design: A retrospective study was performed over a ten-years period from 2007 to 2017 of all fetuses with a first-trimester diagnosis of cystic hygroma. Maternal and fetal parameters were assessed with descriptive statistics.Results: A total of 185 singleton pregnancies were included. Chromosomal anomalies were present in 122 cases (65.9%). Sixty-three fetuses (34.1%) had a normal karyotype. Noonan syndrome was diagnosed in 6 cases using additional testing for RASopathies. In euploid fetuses, a major congenital anomaly was detected in 35 of 63 cases (56%) and if present, 91.4% had an abnormal fetal outcome compared to 32.1% if no structural anomaly was found (p < 0.01). Fetuses with a nuchal translucency thickness more than 10 mm and hydropic fetuses had a worse outcome.Discussion: Associated structural anomalies or hydrops fetalis are significant predictors for an abnormal outcome in pregnancies with first-trimester cystic hygroma and a normal karyotype. Cytogenetic evaluation and detailed sonographic evaluation are of great importance in the determination of the prognosis of pregnancies complicated by first-trimester cystic hygroma. [ABSTRACT FROM AUTHOR]

Advances in prenatal genomics have enabled the assessment of not only the sub-microscopic structure of chromosomes using chromosomal microarray analysis, but also the detection of "pathogenic variants" to the resolution of a single base pair with the use of next generation sequencing. Research is emerging on the additional prenatal diagnostic yield that exome sequencing offers when structural fetal anomalies are detected on ultrasound examination, in particular the identification of monogenic abnormalities defining prognosis and recurrence of anomalies. Primarily assessed using fetal DNA obtained by invasive techniques (amniocytes or chorionic villi), this technology is progressing into a non-invasive approach using maternal plasma. There are several challenges, to be addressed before this technology can be introduced into routine clinical practice. These are primarily technical and interpretational but also relate to service provision; cost-effectiveness; turn-around time; patient acceptability and ethical dilemmas. With adequate pre- and post-test counselling many of these challenges may be overcome and such counselling has to be multi-disciplinary, involving clinical geneticists, genetic scientists, paediatricians, perinatal pathologists and fetal medicine subspecialists. There is therefore a need for obstetricians to have an understanding of the clinical utility, application, advantages and challenges of such technologies before introduction into routine clinical practice. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to make an accurate diagnosis of pyriform sinus fistula (PSF) for prenatal diagnosis.Study Design: Medical records were reviewed for all 35 pyriform sinus fistula patients presenting between 2011 and 2017. Ultrasonography (US), fetal magnetic resonance imaging (MRI) and karyotyping were offered during gestation, while computer tomography (CT) and barium esophagography were performed after birth.Results: Patients included 21 males (60%) and 14 females (40%) with a sex ratio of 1.5:1. The lesion was located on the left side in 32 (91.4%) cases, the right side in 2 (5.7%), and was bilateral (2.8%) in only one case. The sensitivity of CT, MRI, ultrasonography and barium esophagography were 100% (35/35), 69.2% (9/13), 22.9% (8/35), and 80% (20/25), respectively. If the diagnosis was correct, there was almost no recurrence after treatment. Karyotype analysis of all fetuses was normal.Conclusions: Pyriform sinus fistula is more commonly seen in the left side. Compared with ultrasonography, MRI has more advantages in prenatal diagnosis, and it is more accurate in postpartum CT examination. The outcome of children with pyriform sinus fistula may be guarded when it correct diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To assess the longitudinal behavior of Quantitative Lung Index (QLI) for the follow-up of fetuses with congenital diaphragmatic hernia.Study Design: Retrospective study of fetuses with isolated left congenital diaphragmatic hernia. The fetuses were assessed by ultrasound at different gestational ages and QLI was retrospectively calculated by means of previous lung-to-head ratio measurements. We used a random effects model (mixed model with repeated measurements) to compare the performance of the QLI in operated and non-operated fetuses throughout pregnancy.Results: Fifty-eight cases of isolated left diaphragmatic hernia with complete follow-up were assessed in Hospital Universitari Vall d'Hebron in Barcelona (2003-2015). Thirty-eight of them were managed expectantly (non-TO) and the other 20 underwent tracheal occlusion (TO). All fetuses undergoing tracheal occlusion had lung-to-head ratio (LHR) <1, observed-to-expected LHR (o/eLHR) ≤45%, QLI <0.6 and liver up inside the thorax. The survival rate was 87% for the non-TO group and 60% for the TO group (p = 0.02). The QLI remained constant throughout pregnancy in both groups. The QLI in the TO group had lower values than the non-TO group (p < 0.03).Conclusion: The quantitative lung index was constant during pregnancy. This index was lower in fetuses undergoing tracheal occlusion but no significant changes were seen in its performance during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To examine the risk for clinically significant chromosomal microarray analysis (CMA) among fetuses with apparently isolated horseshoe kidney.Methods: Data from all CMA analyses performed due to isolated horseshoe kidney reported to the Israeli Ministry of Health between January 2013 and September 2016 were retrospectively obtained from a computerized database. Risk estimation was performed comparing the rate of abnormal CMA findings to the general population, based on a systematic review encompassing 9272 pregnancies with normal ultrasound, and local data cohort of 5541 pregnancies undergoing CMA due to maternal request.Results: Of 82 pregnancies with isolated horseshoe kidney, one loss-of-copy-number variant compatible with 16p13.11 microdeletion syndrome was demonstrated (1.2%). In addition, two variants of unknown significance (VOUS) were detected (2.4%). The relative risk for pathogenic CMA findings among pregnancies with isolated single horseshoe kidney was not significantly different from the control population (1.03-1.39%).Discussion: To our best knowledge, our study is the first report describing the rate of clinically significant CMA findings in fetuses with isolated horseshoe kidney. The detection of one pathogenic CMA findings in our cohort implies that the value of CMA analysis in such pregnancies is similar to the general population. [ABSTRACT FROM AUTHOR]

Objective: Methods for the antenatal detection of small for gestational age babies (SGA) differ between countries. The aim of this study was to compare the diagnostic accuracy of routine versus selective small for gestational age babies screening policy using data from two European Maternity Units.Study Design: This was a retrospective cohort study from Liverpool Women's Hospital, UK, that uses selective third trimester sonography and from the University Hospital Centre Zagreb, Croatia, that uses routine third trimester sonography for SGA detection. Screen positive cases were defined as pregnancies with estimated fetal weight (EFW) <10th centile at the last 3rd trimester scan. True positives had both EFW and birth weight <10th centile. Pregnancy management data and perinatal outcomes were retrieved from hospital electronic data and special care baby unit (SCBU) reports.Results: The proportion of small for gestational age babies was higher in Liverpool (7.8%) compared with Zagreb (4%); P<0.001. Sensitivity for detection of SGA babies in Zagreb was 27% (95%CI 15%-44%) and 33% (95%CI 23%-45%) in Liverpool. The specificity was high in both centres (Zagreb 100% (95%CI); Liverpool 98% (95%CI)). The induction of labour for antenatally diagnosed SGA babies was more common in Liverpool (38.5%) than in Zagreb (9.1%). In both centres, all antenatally diagnosed SGA babies admitted to SCBU were preterm babies. Their indications for admission to SCBU were complications related to prematurity.Conclusion: The effectiveness of selective SGA screening policy is comparable to universal third trimester ultrasound screening. Further prospective evaluations of SGA screening policies are warranted and they should include full cost-effectiveness analysis and assessment of possible harm from increased interventions leading to more preterm births. [ABSTRACT FROM AUTHOR]

The objective of this study was to review literature about the correlation between fetal autopsy and ultrasound findings of fetal malformations. Search in PubMed, Medline, EMBASE, Clinicl trials.org, reference list was performed. Inclusion criteria for studies selection were: fetal autopsy performed after termination of pregnancy (TOP) or stillbirth, TOP for fetal anomalies, prenatal diagnosis of malformations, data reported as proportional rates.Exclusion Criteria: case reports, non English language, data reported in graphs or percentage. From each article: sample size, type of malformation, indication for TOP, autopsy findings. Fetal anomalies were grouped in central nervous system (CNS), genitourinary (GU), congenital heart defects (CHD), gastrointestinal (GI), thorax, limbs, skeleton, genetics (TOP for abnormal karyotype), multiples (TOP for multiple severe malformations for which a single indication for TOP/stillbirth could not be identified). Correspondence between autopsy and ultrasound was defined as agreement (same diagnosis), additional (additional findings undetected by ultrasound), unconfirmed (false positive and false negative ultrasound). PRISMA guidelines were followed. From 19 articles, 3534 fetuses underwent autopsy, which confirmed prenatal ultrasound in 2401 (68.0%) fetuses, provided additional information in 794 (22.5%) fetuses, and unconfirmed prenatal ultrasound in 329 (9.2%) fetuses. The latter group consisted of 3.2% false positive and 2.8% false negative cases. The additional findings changed the final diagnosis in 3.8% of cases. The most frequent indication for TOP/stillbirth was CNS anomalies (36.3%), whereas thorax anomalies represented the less frequent indication (1.7%). The highest agreement between autopsy and prenatal ultrasound was observed in CNS (79.4%) and genetics (79.2%), followed by GU anomalies (76.6%), skeleton (76.6%), CHD (75.5%), thorax (69.7%); GI (62.6%), multiple (37.0%), limbs (23.3%). In spite of the high agreement between prenatal ultrasound and autopsy, fetal examination is mandatory because in a minority of cases it discloses additional findings or changes the final diagnosis and genetic counselling. [ABSTRACT FROM AUTHOR]

Objective: Atrioventricular septal defect is associated with a high risk of a chromosomal abnormality, particularly trisomy 21. The aim of this study is to assess the rate of trisomy 21 in fetuses diagnosed with an atrioventricular septal defect and to examine the influence of prior screening on the rate of trisomy 21.Methods: Electronic ultrasound database was searched to identify fetuses diagnoses with an atrioventricular septal defect from 2002 to 2014. Rate of trisomy 21 and other aneuploidies was calculated among fetuses with normal situs. The prevalence of trisomy 21 and other aneuploidies was assessed in women with low and high first trimester risk for trisomy 21, using a cut-off value of 1:150 and 1:250.Results: A total 110 fetuses with a diagnosis of atrioventricular septal defect were identified. Among the 98 fetuses with normal situs, the prevalence of trisomy 21 was 46% (95% CI: 36-56%). Using a 1:150 threshold, the rate of trisomy 21 within the low-risk group was 41% (95% CI: 27-57%) while in the high-risk group it was 70% (95% CI: 52-83%), significantly higher than in the low risk group (p=0.028). Similar results were obtained when the 1:250 threshold was applied (66% versus 41%, p=0.055).Conclusions: The rate of trisomy 21 among fetuses identified with an atrioventricular septal defect in the second trimester is high even in those that undergo first trimester combined screening. Some fetuses with a high-risk screening result show a normal karyotype. Therefore, an offer of an invasive procedure to check fetal karyotyping is indicated. Knowledge of these rates may be helpful for parents in the decision making process. [ABSTRACT FROM AUTHOR]

Objectives: To establish a prediction model for fetal congenital heart disease (CHD) that could facilitate selective fetal echocardiography screening for diabetic women, and to provide cost analysis of selective versus global screening of these women.Study Design: A historical cohort study included women with pre-gestational diabetes who received perinatal care at Mayo Clinic, Minnesota from 2007 through 2013. Anatomical scans and fetal echocardiograms were reviewed and charts for postnatal outcomes were abstracted. Logistic regression models were utilized to identify predictors of CHD. Cost of global versus selective screening was estimated using cost per case detected.Results: A cohort of 152 women was included. Abnormal anatomy scan was reported in five (3.3%). Among 51 (33.6%) who had fetal echocardiography, eight (15.7%) had abnormal findings. Postnatal echocardiography was conducted in 36 neonates, 12 had abnormalities. Only first trimester HbA1c was independent predictor with observed incidence of CHD of 1.8, 14.3, and 40% and HbA1c of <8, 8-10, and >10% respectively. Global screening strategy missed 22% of fetal cardiac abnormalities, while selective screening missed 33%.Conclusions: According to our probability model, selective screening based on HbA1c and/or anatomic surveys seems to be an accurate and cost effective strategy for prenatal diagnosis of CHD among diabetic pregnancies. [ABSTRACT FROM AUTHOR]

Objective: Non-invasive prenatal testing (NIPT) is increasingly being used in prenatal aneuploidy screening. The objective of this study was to assess the positive predictive value in our cohort of 68 cases with positive NIPT result. In addition, we wondered if the use of NIPT in cases with ultrasound abnormalities is appropriate, given the limited number of chromosomes investigated.Design: We performed confirmative invasive testing using karyotyping, fluorescence in situ hybridization (FISH) and/or high-resolution chromosomal microarray analysis.Results: In line with the published data, the positive NIPT result was confirmed in 64.7% of cases. Inconclusive and negative NIPT results followed by cytogenetically pathologic findings were encountered in three and in five cases, respectively. Four of the five fetuses with negative NIPT but pathologic cytogenetic findings were born with several malformations and diagnosed right after birth with severe genetic conditions. Of note, in all of those four cases, NIPT was offered despite the finding of major fetal ultrasound abnormalities and despite the fact that the family would not have opposed invasive testing or pregnancy termination.Conclusion: More education of health care providers and caution in counseling and interpretation of test results are needed in order to meet the challenges that this new test, which enriches our diagnostic options in prenatal testing, poses. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to evaluate the clinical characteristics, imaging features, pregnancy complications, prenatal management of patients with placenta chorioangioma. Methods: This was a retrospective study of 26 cases with histologically proven placenta chorioangima, in which the natural history, pregnancy complications, and clinical characteristics including ultrasonography were evaluated. Results: Twelve of the twenty-six cases had a wide range of maternal-fetal complications including polyhydramnios (7), fetal growth restriction (3), fetal distress (2), pre-eclampsia (3), fetal anemia-thrombocytopenia (2), congestive heart failure (1) and fetal abnormality (1). Conclusions: Placenta chorioangioma was associated with series of pregnancy complications such as polyhytramnios, premature delivery, maternal pre-eclampsia, fetal growth restriction, fetal distress, even fetal anemia and cardiomegaly. With regular prenatal examination, necessary treatment, and timely delivery, the majority had a good pregnancy outcome. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether first trimester combined screening for major fetal trisomies is influenced by assisted reproduction techniques from blastocyst transfer, with or without cryopreservation.Study Design: retrospective case-control analysis involving 298 singleton pregnancies with euploid fetuses recruited between 2012 and 2014. Forty-seven women conceived with fresh blastocysts from in vitro fertilization cycles (fresh-blasto), 51 with frozen-thawed blastocysts (frozen-blasto) and 200 were natural conceptions (controls). All cases underwent ultrasound assessment at 11(+0)-13(+6) weeks with measurements of crown rump length, nuchal translucency, free β-hCG and PAPP-A concentrations. The outcome of pregnancy was recorded (gestational age at birth, birth weight, obstetric complications).Results: Baseline characteristics and pregnancy outcomes did not differ substantially among the study groups. The median delta nuchal translucency was significantly higher both in frozen-blasto group (median: 0.27mm; Interquartile Range [IQR]: 0.02-0.44; p<0.001) and in fresh-blasto group (median: 0.17mm; IQR: 0.04-0.39; p=0.014) as compared to control group (median: 0.06mm; IQR: -0.08 to 0.20), whereas it was not different in the frozen-blasto compared to the fresh-blasto group. The median free β-hCG multiples of the median (MoMs) was significantly higher both in frozen-blasto group (median 1.15; IQR 0.83-2.11; p=0.001) and in fresh-blasto group (median 0.95; IQR 0.52-1.48; p=0.001) as compared to control group (median 0.99; IQR 0.57-1.26), and it was also higher in frozen-blasto group compared to fresh-blasto group (p<0.001). The three groups showed no significant differences in the median PAPP-A MoMs. The median delta crown rump length was also not significantly different among the three groups.Conclusions: in assisted reproduction technique pregnancies from blastocyst transfer, with or without cryopreservation, both the nuchal translucency measurement and free β-hCG concentration are higher as compared to spontaneous conceptions, whereas PAPP-A does not show any significant difference. These features are apparently unrelated to the outcome of pregnancy and may be due to alterations or delays in embryogenesis or placentation with potential relevance for the screening test performance. [ABSTRACT FROM AUTHOR]

Objective: To assess the clinical value of prenatal diagnosis of fetuses with increased nuchal translucency (NT) using an approach based on quantitative fluorescent polymerase chain reaction (QF-PCR) and chromosomal microarray (CMA).Study Design: From January 2013 to October 2014, we included 175 pregnancies with fetal NT ≥ 3.5mm at 11-13 weeks' gestation who received chorionic villus sampling. QF-PCR was first used to rapidly detect common aneuploidies. The cases with a normal QF-PCR result were analyzed by CMA.Results: Of the 175 cases, common aneuploidies were detected by QF-PCR in 53 (30.2%) cases (30 cases of trisomy 21, 12 cases of monosomy X, 7 cases of trisomy 18, 3 cases of trisomy 13 and 1 case of 47, XXY). Among the 122 cases with a normal QF-PCR result, microarray detected additional pathogenic copy number variants (CNVs) in 5.7% (7/122) of cases. Four cases would have expected to be detectable by conventional karyotyping because of large deletions/duplications (>10 Mb), leaving three cases (2.5%; 3/118) with pathogenic CNVs only detectable by CMA.Conclusion: It is rational to use a diagnostic strategy in which CMA is preceded by the less expensive, rapid, QF-PCR to detect common aneuploidies. CMA allows detection of a number of pathogenic chromosomal aberrations in fetuses with a high NT. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of the sonographic cardiothoracic ratio (CTR) in early pregnancy for the prediction of fetal haemoglobin (Hb) Bart's disease.Study Design: Over a 1.5-year period at a Chinese tertiary obstetric centre, women at risk of Hb Bart's disease were given the option of a non-invasive approach to exclude an affected pregnancy between 11 weeks and 13 weeks and 6 days of gestation, with a routine rescan after a 2-week interval. The fetal CTR, a sonographic marker, was assessed, and invasive testing followed in cases of fetal cardiomegaly. The diagnosis of fetal Hb Bart's disease was based on DNA analysis from chorionic villus sampling.Results: Of 154 at-risk cases studied, five cases (four at 11 weeks of gestation) were subjected to direct invasive testing because of an unsatisfactory scan. Of the remaining 149 cases, non-invasive ultrasound examinations were performed successfully. Thirty-four (22.8%) affected pregnancies were revealed, including one picked up on rescan. The sensitivity and specificity of the non-invasive approach were 97.1% and 100%, respectively. The need for an invasive test was reduced by 74.7%, and all affected pregnancies except one were diagnosed before 14 weeks of gestation.Conclusion: CTR can differentiate reliably between pregnancies with and without Hb Bart's disease. This non-invasive approach for the exclusion of Hb Bart's disease can be used in early pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To present the experience on prenatal diagnosis of Wolf-Hirschhorn syndrome (WHS) to further delineate the fetal presentation of this syndrome.Study Design: This was a retrospective analysis of ten pregnancies with fetal WHS identified by chromosomal microarray (CMA). Clinical data were reviewed for these cases, including maternal demographics, indications for invasive testing, sonographic findings, CMA results and pregnancy outcomes.Results: Three cases were diagnosed at the first trimester because of an increased NT or cystic hygroma. The remaining seven cases were identified at late gestation for abnormal ultrasound findings. CMA revealed 4p deletions to be terminal in all of the ten cases. Deletion sizes ranged from 2.05 to 19.02 Mb.Conclusion: Prenatal findings such as increased NT, severe and early onset intrauterine growth retardation, and renal dysplasia or oligohydramnios should warrant the diagnosis of WHS and invasive testing using CMA. [ABSTRACT FROM AUTHOR]

Objective: To describe any trends in the uptake of antenatal screening for Down's syndrome since the addition of the earlier first trimester combined test. Study Design: All antenatal screening tests for Down's syndrome were carried out and their results were recorded by the Clinical Biochemistry Department at the Hull Royal Infirmary (HRI) and reviewed against the antenatal booking data held at the Women and Children's Hospital at HRI. The uptake of antenatal Down's syndrome screening for 5 different age groups of women across a four-year-period from 2007 to 2010 was analysed. Results: There was a significant increase in uptake of antenatal screening for Down's syndrome from 43.9% to 56.5% after the introduction of the combined test in 2010. This increase was apparent in all age groups. There was no change in the proportion of women opting for an invasive test following a positive screening test. Conclusion: Addition of the earlier first trimester combined test has increased uptake of antenatal screening for Down's syndrome in women of all ages. This is most likely due to the advantages this test gives women such as earlier decision making, earlier further invasive diagnostic testing and earlier termination, if necessary. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To compare 35 commonly used formulae for small and average sized fetuses on their accuracy in estimating the birth weight in fetuses of 1500g or less. Study design: For this retrospective study a database search was performed for all singleton pregnancies without structural or chromosomal defects and with a birth weight of 1500g or less where the last ultrasound examination was performed within seven days before delivery. Percentage error and absolute percentage error were calculated based on 35 different weight estimation formulae. Multiple regression analysis was used to determine the significant contributors to the absolute percentage error. Results: One hundred and ninety-three cases fulfilled the inclusion criteria. The median birth weight was 990g. The percentage error ranged between −15.2% (underestimation with the Merz I formula) and 37.4% (overestimation with the Jordaan formula) and the respective standard deviations between 10.5% (Mielke I) and 54.0% (Schillinger), respectively. The absolute percentage error was between 8.5% and 37.6%. The most accurate weight estimation was achieved with the formula from Mielke (percentage error 1.8% and absolute percentage error 8.5%). Multiple regression analysis showed that significant contributors to the percentage error of the Mielke formula were biparietal diameter (OR=−0.206, p =0.045), occipitofrontal diameter (OR=0.765, p <0.0001), abdominal circumference (OR=−2.953, p<0.0001), femur length (OR=−0.903, p <0.0001), head to abdomen ratio (OR=−1.080, p <0.0001) and fetal weight (OR=2.847, p <0.0001). Conclusion: When estimating fetal weight in fetuses weighing 1500g or less, one has to be aware of the great differences in accuracy among the formulae. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the prenatal ultrasound (US) score can effectively differentiate fetal physiological and pathological hydronephrosis. Study Design: 158 fetuses (198 kidneys) with hydronephrosis (PAPD>or=10mm) were diagnosed by prenatal US in the third trimester. We measured and recorded three US parameters: renal pelvic anterior posterior diameter (PAPD), renal parenchyma thickness and pelvicaliceal morphology. They were graded with a score from 0 to 3 on the basis of severity of hydronephrosis, and the total US score of each kidney was obtained. According to the postnatal US and clinical diagnosis and management, all the cases were divided into two groups: physiological and pathological hydronephrosis. Using receiver operating characteristic curves analysis, we researched whether the US score was more accurate than each parameter and which was the best cut-off value for differential diagnosis of physiological and pathological hydronephrosis. Results: Of all the 198 hydronephrosis, 139 (70.20%) were physiological and 59 (29.80%) were pathological confirmed postnatally. Area under the curve of US score was 0.982, which was significantly larger than that of each parameter (P<0.05). The higher the score, the higher the possibility of pathological hydronephrosis was. Score 6 was the best cut-off value: the sensitivity, specificity, positive predictive value, negative predictive value, consistency rate and Youden's index were 89.83%, 94.24%, 86.89%, 95.62%, 92.93% and 0.8407, respectively. Conclusion: Prenatal US score is easy to obtain by measuring some data of the kidney and can effectively differentiate fetal physiological and pathological hydronephrosis. It can also be used as a new quantitative method to evaluate the prognosis of fetal hydronephrosis so as to provide reference for prenatal intervention and more accurate information for the family of the fetus. [ABSTRACT FROM AUTHOR]

Objectives: To establish in infants with gastroschisis whether outcome is different when comparing a prenatal diagnosis with a diagnosis only at birth with the intention to develop a prenatal surveillance protocol. Intestinal atresia established after birth and preterm versus term delivery were studied as risk factors. Study Design: All 24 fetuses and 9 infants diagnosed with gastroschisis and referred to our tertiary center between January 1991 and June 2003 were studied retrospectively. Results: The infants of the prenatal subset delivered at our tertiary center and 18 survived. There were two pregnancy terminations, three intrauterine deaths at 19, 33 and 36 weeks respectively and one neonatal death. All nine infants in the postnatal subset survived. Eight were out born and one was delivered at our tertiary center. Prenatal bowel dilatation did not correlate with outcome. Between the prenatal and postnatal subset no significant difference in outcome of live-born infants was established. For four infants with intestinal atresia a significant difference was demonstrated for induction of preterm labour (P<0.05), duration of parenteral nutrition (P<0.01), number of additional surgical procedures (P<0.001) and length of hospital stay (P<0.01). The fifteen infants born prior to 37 weeks of gestation spent a significantly longer period in hospital compared to those delivered at term. When the cases with bowel atresia were excluded this difference was no longer present. Five of the 33 cases were diagnosed with associated anomalies which mainly involved the urinary tract. Conclusion: Neonatal outcome of live born infants following a prenatal diagnosis of gastroschisis is not different from a diagnosis at birth. The presence of intestinal atresia is the most important prognostic factor for morbidity. The supplemental value of prenatal diagnosis to the outcome of infants with gastroschisis may be in the prevention of unnecessary intrauterine death and detection of intestinal complications. A proposed surveillance protocol for fetuses with gastroschisis focused on intrauterine signs of pending distress such as a dilated stomach, intra abdominal bowel dilatation with peristalsis, notches in the umbilical artery Doppler signal, development of polyhydramnios and an abnormal CTG registration may improve outcome. [ABSTRACT FROM AUTHOR]

Objectives: To describe the natural history of pyelectasis from its detection in the second trimester to delivery, its capability to predict renal pathology and whether prenatal development of pelvic dilatation is correlated to its postnatal evolution. Study Design: A retrospective analysis involving 375 fetuses with a complete urological follow-up. Prenatal ultrasound was correlated with the results of postnatal investigation and frequency of postnatal surgery was established. Results: Two-hundred and eighty cases underwent at least two examinations before birth. 73.1% were male fetuses. 57.4% had a bilateral pyelectasis. Prenatal evolution of pelvic dilatation was the following:18.6% of the cases normalized, in 34.6% of the cases the dilatation reduced but did not disappear, in 30.7% it remained unchanged, while it worsened in 16.4%. One case from the first group, three cases from the second, seven cases from the third and 11 cases from the fourth needed surgical treatment. 1.9, 7.2, 18.6, 23.9% of cases respectively worsened after birth in the four groups (trend: P=0.001). Conclusions: Prenatal diagnosis of pyelectasis improves the outcome of these children due to a surgical approach that avoids renal damage. There is a good correlation between prenatal evolution and postnatal outcome, although a postnatal follow-up is opportune in those cases that normalized before birth. [ABSTRACT FROM AUTHOR]

Dicephalus twinning is an extremely rare type of conjoined twins. Early prenatal diagnosis of this condition is important to provide an opportunity for pregnancy termination. We present such a case, which was diagnosed by ultrasound examination at 12 weeks of gestation. The ultrasonographic criteria are discussed together with implications for management. [ABSTRACT FROM AUTHOR]

Acardiac twins are usually diagnosed during the antenatal period and almost invariably cause complications to the other fetus. In this case, an acardiac twin pregnancy was misdiagnosed antenatally as a degenerated myoma but ended with delivery of a healthy baby. [Copyright &y& Elsevier]